Field of the Invention
This invention is directed to new organic compounds and is particularly concerned with a process for 2-(4H- 1,2,4-triazol-4-yl)benzophenones.
The novel compounds and the process of production therefore can be illustratively represented as follows: ##STR2##
The more desirable compounds in this invention are those of the formula: ##STR3## wherein R' is hydrogen or methyl; wherein R'.sub.2 is hydrogen, chloro, or fluoro; wherein R'.sub.3 is hydrogen, or fluoro if R'.sub.2 is fluoro; and wherein R'.sub.4 is hydrogen, fluoro, chloro, or trifluoromethyl.
The most desirable products are of the formula: ##STR4## wherein R'.sub.2 is hydrogen, chloro, or fluoro; and wherein R'.sub.3 is hydrogen, or fluoro if R.sub.2 is fluoro.
The products of formula IV are useful per se as tranquilizers but their principal use is as intermediates for compounds of formula VII which are extremely potent tranquilizers. The compounds of formula VII are obtained from those of formula IV by the following scheme: ##STR5##
The process of this invention comprises:
1. Refluxing a 2-chloro-4-phenylquinoline (1) with hydrazine hydrate to give a 2-hydrazino-4-phenylquinoline (II);
2. refluxing the 2-hydrazino-4-phenylquinoline (II) with a trialkyl orthoacylate e.g. with triethyl orthoformate, triethylorthoacetate, triethyl orthopropionate or trimethyl orthobutyrate, in an inert organic solvent, to give the corresponding 1-substituted-5-phenyl-s-triazolo-[ 4,3-a]quinoline (III);
3. treating III with an oxidizing agent or system such as ruthenium dioxide and sodium periodate or ozone in an inert solvent at low temperature to give a mixture containing mainly a 2-(3-substituted-4H- 1,2,4-triazol-4-yl)benzophenone (IV) and a 4-(2-benzoylphenyl)-5-substituted-4H- 1,2,4-triazolo-3-carboxaldehyde;
The synthetic steps to produce from intermediates of formula IV the final products, comprises:
4. treating (IV) with formaldehyde to obtain a 2-[3-(hydroxymethyl)-5-substituted-4H- 1,2,4-triazol-4-yl]benzophenone (V).
5. converting alcohol (V) to a halide with a halogenating agent such as phosphorus tribromide, phosphorus oxychloride, phosphorus triiodide, or thionyl chloride to obtain the corresponding 2-[3-(halomethyl)-5-substituted-4H- 1,2,4-triazol-4-yl]benzophenone (VI); and
6. treating (VI) with ammonia to give the corresponding 1-substituted-6-phenyl-4H-s-triazolo[ 4,3-a][ 1,4]benzodiazepine VII.